tbuckley/cabot-search huggingface dataset:
Health, Pesticide Adjuvants, and Inert Ingredients: California Case Study Illustrates Need for Data Access
Authors: Caroline Cox, Michael Zeiss
Journal: Environmental Health Perspectives (2022)

Background: Many pesticide products are mixtures of multiple chemicals. These include active ingredients intended to kill pests, and so-called inert ingredients intended to improve the physical characteristics of the product. In addition, shortly before applying a pesticide product, applicators often mix adjuvants into the sprayer tank. Adjuvants are products designed to improve the performance or physical properties of a pesticide spray mixture. Manufacturers may use a particular chemical compound both as an inert ingredient within pesticide products and as a component of adjuvant products. Nonetheless, regulations dictate that data on use are publicly available only for the portion used in adjuvants. Adjuvants are exempt from federal registration, but are defined as pesticides in California. Based on that definition, California has identified α-(p-nonylphenyl)-ω-hydroxypoly(oxyethylene) (APNOHO) as the most widely used pesticide in the state, applied to more than 10 million acres annually. That quantified use includes only agricultural acres treated with adjuvants containing APNOHO. Total APNOHO use is likely higher because manufacturers also use the chemical as an inert ingredient within pesticide products, although data on such use are shielded by regulation. Objectives: We use APNOHO as a case study to demonstrate that the use of adjuvants and inert ingredients is difficult to track because relevant information is not publicly available. We synthesize information that suggests widespread agricultural use of alkylphenol ethoxylates, such as APNOHO, may pose significant human and environmental health risks. We then make recommendations for future research and policy. Methods: We used information from California's pesticide use reporting system and the U.S. Environmental Protection Agency (EPA) to estimate use of APNOHO. We used U.S. EPA and European databases, as well as published research, to identify human and environmental health hazards of APNOHO. We focused on research showing that APNOHO is an endocrine-disrupting chemical. Discussion: Within California, APNOHO is applied in more than 150 adjuvant products. Nationwide, it is used as an inert ingredient in at least 650 pesticide products. Exposure to APNOHO is associated with endocrine disruption, birth defects, and aquatic toxicity. We suggest that the case of APNOHO illustrates the larger problem of a lack of publicly available data on use and toxicity of many adjuvants and pesticide inert ingredients. We recommend that researchers and regulators include adjuvants and inert ingredients when evaluating pesticide hazards, including endocrine disruption. We also recommend regulatory requirements to identify all ingredients on product labels. https://doi.org/10.1289/EHP10634
Interpenetrating Polymer Network Hydrogels Formed Using Antibiotics as a Dynamic Crosslinker for Treatment of Infected Wounds (Adv. Healthcare Mater. 15/2022)
Authors: Mengjing Fu, Yingying Gan, Fenglin Jiang, Xue Lv, Nathanael Tan, Xiaomiao Zhao, Yi Yan Yang, Peiyan Yuan, Xin Ding
Journal: Advanced Healthcare Materials (2022)
Body Temperature Enhanced Adhesive, Antibacterial, and Recyclable Ionic Hydrogel for Epidermal Electrophysiological Monitoring (Adv. Healthcare Mater. 15/2022)
Authors: Ying Liu, Chan Wang, Jiangtao Xue, Guanhua Huang, Shuang Zheng, Ke Zhao, Jing Huang, Yiqian Wang, Yan Zhang, Tailang Yin, Zhou Li
Journal: Advanced Healthcare Materials (2022)

Electrophysiological Monitoring A multifunctional ionic hydrogel based on dual physical cross-linked networks helps build a highly compliant and gapless interface with the skin, as described by Tailang Yin, Zhou Li, and co-workers in article number 2200653. When applied as the epidermal electrode, it shows good capability to record multifarious electrophysiological signals with high signal-to-noise ratio and ultra-low detection limit.
Magnesium Oxide/Poly(<scp>l</scp>‐lactide‐co‐<i>ε</i>‐caprolactone) Scaffolds Loaded with Neural Morphogens Promote Spinal Cord Repair through Targeting the Calcium Influx and Neuronal Differentiation of Neural Stem Cells (Adv. Healthcare Mater. 15/2022)
Authors: Jile Xie, Jiaying Li, Jinjin Ma, Meimei Li, Xingran Wang, Xinya Fu, Yanxia Ma, Huilin Yang, Bin Li, None Saijilafu
Journal: Advanced Healthcare Materials (2022)

Spinal Cord Injury In article number 2200386, by Bin Li, Saijilafu, and co-workers, a novel purmorphamine (PUR)/retinoic acid (RA)-loaded MgO/PLCL scaffold for repairing spinal cord injury is developed. The magnisum ions released from MgO nanoparticles protect the neurons and the PUR/RA promotes the recruitment and neuronal differentiation of endogenous neural stem cells.
Snake Venom Hydrogels as a Rapid Hemostatic Agent for Uncontrolled Bleeding (Adv. Healthcare Mater. 15/2022)
Authors: Ramanathan Yegappan, Jan Lauko, Zhao Wang, Martin F. Lavin, Amanda W. Kijas, Alan E. Rowan
Journal: Advanced Healthcare Materials (2022)

Snake Venom Hydrogels Death from uncontrolled bleeding is considered preventable. Taking the innovation from nature, Amanda W. Kijas, Alan E. Rowan, and co-workers, in article number 2200574, employ proteins from snake venom to both accelerate clotting and retain a stable blood clot delivered with a topically applied thermoresponsive hydrogel to seal the wound. This achieves striking reductions in both blood loss and clotting time, in addition to overcoming dysfunctional blood coagulation arising from blood thinner medication. Cover image made by Alex Kakinen Studio.
An Optimally Fabricated Platform Guides Cancer‐Specific Activation of Chemotherapeutic Drugs and Toxicity‐Free Cancer Treatment (Adv. Healthcare Mater. 15/2022)
Authors: Ok Jeong Moon, Chul Joo Yoon, Bo‐Ram Lee, Jeewon Lee
Journal: Advanced Healthcare Materials (2022)

Cancer Chemotherapy In article number 2200765 by Jeewon Lee and co-workers, optimized structures to enable cancer cell-specific activation of chemotherapeutic drugs are constructed through integrating core peptide units into highly-ordered, stable, and guest-adaptable structures of human heavy chain ferritin (huHF) scaffolds. After endocytosis to cancer and normal cells, the drugs are released from huHF-drug conjugates in cancer cells, whereas in normal cells, the huHF-drug conjugates remain inactive without drug release.
Editorial Board and Contents
Authors: Moran Furman, Paige Shaklee, Fred Kop, Ria Otten, Patrick Scheffmann, Silvia Arber, Anders Björklund, J Paul Bolam, Sarah Bottjer, Rui Costa, Ann Marie, Craig Barry, J Dickson, Chris Doe, Craig Garner, Yukiko Goda, Kenneth Harris, Nancy Ip, Meyer Jackson, Maria Karayiorgou, Robert Malenka, Mark Mattson, Freda Miller, Richard Morris, Maiken Nedergaard, Eric Nestler, Anna Roe, Hitoshi Sakano, Greg Stuart, Marc Tessier-Lavigne, Chris Walsh
Journal: Trends in Neurosciences (2018)
Enhanced effect of combining bone marrow mesenchymal stem cells (BMMSCs) and pulsed electromagnetic fields (PEMF) to promote recovery after spinal cord injury in mice
Authors: Liyi Huang, Xin Sun, Lu Wang, Gaiqing Pei, Yang Wang, Qing Zhang, Zejun Liang, Dong Wang, Chenying Fu, Chengqi He, Quan Wei
Journal: MedComm (2022)

Spinal cord injury (SCI) is a destructive traumatic disease of the central nervous system without satisfying therapy efficiency. Bone marrow mesenchymal stem cells (BMMSCs) therapy promotes the neurotrophic factors' secretion and axonal regeneration, thereby promoting recovery of SCI. Pulsed electromagnetic fields (PEMF) therapy has been proven to promote neural growth and regeneration. Both BMMSCs and PEMF have shown curative effects for SCI; PEMF can further promote stem cell differentiation. Thus, we explored the combined effects of BMMSCs and PEMF and the potential interaction between these two therapies in SCI. Compared with the SCI control, BMMSCs, and PEMF groups, the combinational therapy displayed the best therapeutic effect. Combinational therapy increased the expression levels of nutritional factors including brain-derived neurotrophic factor (BDNF), nerve growth factors (NGF) and vascular endothelial growth factor (VEGF), enhanced neuron preservation (NeuN and NF-200), and increased axonal growth (MBP and myelin sheath). Additionally, PEMF promoted the expression levels of BDNF and VEGF in BMMSCs via Wnt/β-catenin signaling pathway. In summary, the combined therapy of BMMSCs and PEMF displayed a more satisfactory effect than BMMSCs and PEMF therapy alone, indicating a promising application of combined therapy for the therapy of SCI.
Racial and ethnic differences in tumor characteristics and overall survival of women with melanoma: A national cancer database retrospective cohort study
Authors: Jennifer M. Fernandez, Bianka N. Bubic, Sabrina Dahak, Elizabeth M. Mata, Kevin R. Kwan, Adam Sutton, Melodi Javid Whitley, Ashley Wysong
Journal: Journal of the American Academy of Dermatology (2022)
Highlights of This Issue
Journal: Clinical Cancer Research (2018)

Plasma-based comprehensive tumor genotyping expands access to standard-of-care precision oncology to patients previously ineligible due to barriers associated with tissue sampling. Despite this, comprehensive and clinically relevant validation studies are lacking, which leaves clinicians unable to properly vet and interpret available options. Odegaard and colleagues describe definitive analytical and clinical validation studies of a comprehensive tumor-derived cell-free DNA sequencing assay for clinical genotyping of advanced solid tumors and report experience applying this technology in the clinical care of 10,593 consecutive patients. These data establish this technology as a clinically effective and accurate tumor genotyping alternative for patients for whom tissue genotyping is infeasible.Current platforms to explore the genomic causes of primary or acquired resistance to cancer therapies rely on the analysis of DNA from tumor samples. Toledo and colleagues applied a blood-based, tumor-free genomic strategy based on whole-exome sequencing of germline and plasma cell-free DNA from a refractory metastatic colorectal cancer patient and identified a somatic KDR/VEGFR2 mutation located at the entrance of the receptor's ATP-binding pocket domain. The authors validated their findings in vitro and in vivo to show that therapy modulating KDR/VEGFR2 somatic mutations occur in 1% to 3% of samples across tumor types.Clinical gains that have been observed using immune checkpoint agents in a wide array of malignancies have, unfortunately, not translated to glioblastoma. Through integrative cross-platform analyses, Kesarwani and colleagues demonstrate that aberrant tryptophan metabolism represents a metabolic node in glioblastoma and serves as an immune checkpoint. Importantly, although targeting this metabolic pathway using an agent capable of crossing the blood brain barrier has no antitumor activity alone, potent sensitization is observed when combined with radiation by mitigating radiation-induced immune checkpoint reactivation. These findings offer a framework for novel combinatorial strategies that may be tested clinically in this otherwise recalcitrant tumor.Mutations in HOXB13 highlights HOX protein regulation as a critical factor in prostate cancer initiation and progression. HOX proteins, however, depend upon their cofactors to regulate transcriptional specificity and function. Bhanvadia and colleagues show that expression of the HOX cofactors MEIS1 and MEIS2 renders prostate tumors more indolent by regulating pathways involved in cMYC signaling, cell proliferation, cell adhesion, and cell differentiation. These data suggest that MEIS-positive prostate tumors represent a less-aggressive form of prostate cancer.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2018)

Adipocytes and MelanomaMelanomas arise from melanocytes at the dermal-epidermal junction of the skin.Tumors progress through vertical growth, past the dermis into subcutaneous tissue.Zhang and colleagues show that adipocytes in subcutaneous tissues transfer lipids directly to melanoma cells.Lipids are transferred through surface FATP/SLC27A lipid transporters, resulting in altered tumor cell metabolism.Melanomas significantly overexpress FATP1/SLC27A1, and FATP1 expression cooperated with BRAF V600E in transgenic zebrafish and in mouse xenografts to accelerate melanoma.Pharmacologic blockade of FATPs with the small-molecule Lipofermata abrogated lipid transport into melanoma cells and reduced melanoma growth and invasion.
Endoscopy International Open – recently published
Journal: Endoscopy (2018)

Comment on: Endosonography-guided drainage of loculated malignant ascites using double-pigtail plastic stentsEndosc Int Open 2018; 06(07): E902-E906DOI: 10.1055/a-0605-3587 Comment on: Endoscopic ultrasound-guided coil and glue for treatment of splenic artery pseudo-aneurysm: new kid on the block!Endosc Int Open 2018; 06(07): E821-E825DOI: 10.1055/a-0608-4402 Comment on: Open-pore film drainage (OFD): a new multipurpose tool for endoscopic negative pressure therapy (ENPT)Endosc Int Open 2018; 06(07): E865-E871DOI: 10.1055/a-0599-5886
Methylome decoding of RdDM-mediated reprogramming effects in the Arabidopsis MSH1 system
Authors: Hardik Kundariya, Robersy Sanchez, Xiaodong Yang, Alenka Hafner, Sally A. Mackenzie
Journal: Genome biology (2022)

Abstract Background Plants undergo programmed chromatin changes in response to environment, influencing heritable phenotypic plasticity. The RNA-directed DNA methylation (RdDM) pathway is an essential component of this reprogramming process. The relationship of epigenomic changes to gene networks on a genome-wide basis has been elusive, particularly for intragenic DNA methylation repatterning. Results Epigenomic reprogramming is tractable to detailed study and cross-species modeling in the MSH1 system, where perturbation of the plant-specific gene MSH1 triggers at least four distinct nongenetic states to impact plant stress response and growth vigor. Within this system, we have defined RdDM target loci toward decoding phenotype-relevant methylome data. We analyze intragenic methylome repatterning associated with phenotype transitions, identifying state-specific cytosine methylation changes in pivotal growth-versus-stress, chromatin remodeling, and RNA spliceosome gene networks that encompass 871 genes. Over 77% of these genes, and 81% of their central network hubs, are functionally confirmed as RdDM targets based on analysis of mutant datasets and sRNA cluster associations. These dcl2/dcl3/dcl4 -sensitive gene methylation sites, many present as singular cytosines, reside within identifiable sequence motifs. These data reflect intragenic methylation repatterning that is targeted and amenable to prediction. Conclusions A prevailing assumption that biologically relevant DNA methylation variation occurs predominantly in density-defined differentially methylated regions overlooks behavioral features of intragenic, single-site cytosine methylation variation. RdDM-dependent methylation changes within identifiable sequence motifs reveal gene hubs within networks discriminating stress response and growth vigor epigenetic phenotypes. This study uncovers components of a methylome “code” for de novo intragenic methylation repatterning during plant phenotype transitions.
Survey of the binding preferences of RNA-binding proteins to RNA editing events
Authors: Xiaolin Hu, Qin Zou, Li Yao, Xuerui Yang
Journal: Genome biology (2022)

Adenosine-to-inosine (A-to-I) editing is an important RNA posttranscriptional process related to a multitude of cellular and molecular activities. However, systematic characterizations of whether and how the events of RNA editing are associated with the binding preferences of RNA sequences to RNA-binding proteins (RBPs) are still lacking.
BASS: multi-scale and multi-sample analysis enables accurate cell type clustering and spatial domain detection in spatial transcriptomic studies
Authors: Zheng Li, Xiang Zhou
Journal: Genome biology (2022)

Spatial transcriptomic studies are reaching single-cell spatial resolution, with data often collected from multiple tissue sections. Here, we present a computational method, BASS, that enables multi-scale and multi-sample analysis for single-cell resolution spatial transcriptomics. BASS performs cell type clustering at the single-cell scale and spatial domain detection at the tissue regional scale, with the two tasks carried out simultaneously within a Bayesian hierarchical modeling framework. We illustrate the benefits of BASS through comprehensive simulations and applications to three datasets. The substantial power gain brought by BASS allows us to reveal accurate transcriptomic and cellular landscape in both cortex and hypothalamus.
Racial, Ethnic, and Socioeconomic Disparities in Treatment Delay Among Patients With Hepatocellular Carcinoma in the United States
Authors: Nikita Sandeep Wagle, Sulki Park, David Washburn, Robert L. Ohsfeldt, Nicole E. Rich, Amit G. Singal, Hye-Chung Kum
Journal: Clinical Gastroenterology and Hepatology (2022)
Radiation enhances the efficacy of EGFR-targeted CAR-T cells against triple-negative breast cancer by activating NF-κB/Icam1 signaling
Authors: Min Zhou, Muhua Chen, Bizhi Shi, Shengmeng Di, Ruixin Sun, Hua Jiang, Zonghai Li
Journal: Molecular Therapy (2022)

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, with limited treatment options. Epidermal growth factor receptor (EGFR) is reported to be expressed in 50%-75% of TNBC patients, making it a promising target for cancer treatment. Here we show that EGFR-targeted chimeric antigen receptor (CAR) T cell therapy combined with radiotherapy provides enhanced antitumor efficacy in immunocompetent and immunodeficient orthotopic TNBC mice. Intriguingly, this combination therapy resulted in a substantial increase in the number of tumor-infiltrating CAR-T cells. The efficacy of this combination was independent of tumor radiosensitivity and lymphodepleting preconditioning. Cytokine profiling showed that this combination did not increase the risk of cytokine release syndrome (CRS). RNA sequencing (RNA-seq) analysis revealed that EGFR-targeting CAR-T therapy combined with radiotherapy increased the infiltration of CD8+ T and natural killer (NK) cells into tumors. Mechanistically, radiation significantly increased Icam1 expression on TNBC cells via activating nuclear factor κB (NF-κB) signaling, thereby promoting CAR-T cell infiltration and killing. These results suggest that CAR-T therapy combined with radiotherapy may be a promising strategy for TNBC treatment.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2018)

Genetic variability among cancer cells within a single tumor impacts biomarker status and treatment resistance.Karlsson and colleagues hypothesized that different anatomical regions within the same primary tumor at the same time can exhibit distinct evolutionary trajectories of individual clones.They mapped the prevalence of genetically distinct clones over 250 regions in 54 childhood patients with neuroblastoma, Wilms' tumor, and rhabdomyosarcoma.Their work showed that different anatomic areas within a primary tumor simultaneously follow up to four evolutionary trajectories.The fourth and rarest pattern is the local emergence of a myriad of clones with p53 inactivation.
Highlights of This Issue
Journal: Clinical Cancer Research (2018)

Many cancer patients do not respond to immunotherapy, and new strategies are needed to overcome resistance. To explore molecular mechanisms of resistance to immunotherapy, Huang and colleagues performed a screen using patient-derived melanoma cells and autologous TILs, and they identified the RNA-binding protein MEX3B as a novel target associated with immunoresistance. MEX3B binds to HLA-A 3′ UTR and destabilizes HLA-A mRNA, thus downregulating HLA-A expression and blocking tumor recognition by T cells. These findings may lead to the development of therapeutic strategies targeting MEX3B, in the hope of overcoming immunoresistance and achieving better clinical outcomes for melanoma patients treated with immunotherapy.PD1 receptor is a known negative regulator of T lymphocytes. Sanlorenzo and colleagues explored the biological relevance of PD1 directly expressed by melanoma cells, where it can promote tumor growth. Under baseline conditions, PD1 was consistently expressed by melanoma at very low levels, and its blockade did not have a relevant effect on tumor growth; however, upon treatment with BRAF and MEK inhibitors (BRAF/MEKi), the rates of PD1+ melanoma cells significantly increased. In a preclinical immunodeficient model, the blockade of PD1 on melanoma cells prolonged the response to BRAF/MEKi and delayed tumor relapse, supporting the basis for a lymphocyte independent synergism.Through analyzing the copy number profiles of 10,759 tumor genomes of 31 cancer types, Ye and colleagues found the type-I interferon, α- and β-defensin genes were homozygously deleted in 19 cancer types with high frequencies. Deletion of interferon and defensin genes activated oncogenic and cell cycle pathways while repressed immune response pathways. Importantly, these homozygous deletions associated with shortened overall or disease-free survival in a number of cancer types and the anti-CTLA-4 immunotherapy resistance in metastatic melanoma patients. This study reveals the deletion of interferon/defensin as potential prognostic and predictive biomarker for immunotherapy resistance.Claret and colleagues explored model-based estimates of on-treatment growth rate constant to predict overall survival (OS) benefit (hazard ratio) with atezolizumab versus docetaxel in NSCLC. A multivariate OS model was developed based on phase II POPLAR study and externally validated in predicting phase III study OAK OS HR (in all comers as well as by PD-L1 expression) based on early tumor kinetic data (40 weeks) before OS maturation. In both studies, PFS was similar between arms. On-treatment growth rate constant is proposed as an early endpoint to support decisions in cancer immunotherapy studies.
Unbowed, unbent, unbroken: predicting pulmonary hypertension using echocardiography
Authors: Mariëlle C. van de Veerdonk, Anton Vonk-Noordegraaf, Jean-Luc Vachiery
Journal: European Respiratory Journal (2022)

During the first meeting of the World Health Organization (WHO) in 1973, pulmonary hypertension (PH) was defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg measured by right heart catheterisation [1]. This criterion was chosen arbitrarily and was founded on the premise that mPAP at rest in a supine position does not exceed 15 mmHg 2]. In 2009, the landmark paper of Kovacs et al . [3] provided scientific evidence for this statement and showed that normal mPAP at rest was 14 mmHg, with an upper limit of normal of 20 mmHg. In addition, accumulating data has indicated that patients with mPAP ≥19 mmHg but below the haemodynamic threshold of 25 mmHg are at increased mortality risk [4–6]. The probability of pulmonary hypertension can accurately be estimated by current echocardiographic criteria <https://bit.ly/3KMCWQ2> We thank Linda Grutterink, senior sonographer at the Department of Cardiology, Amsterdam UMC, Amsterdam, the Netherlands, for the contribution of the echocardiographic images.
A step forward for an intermediate cystic fibrosis population
Authors: Susan E. Birket
Journal: European Respiratory Journal (2022)

<b>Thao Nguyen-Khoa and colleagues investigated the benefit of using beta-adrenergic (β-adr) sweat secretion (SST) measured by evaporimetry to determine the CFTR functional status, an important report that presents a useful novel method.</b>https://bit.ly/3MEsHhc
Disease State Transition Probabilities Across the Spectrum of NAFLD: A Systematic Review and Meta-Analysis of Paired Biopsy or Imaging Studies
Authors: Phuc Le, Julia Yang Payne, Lu Zhang, Abhishek Deshpande, Michael B. Rothberg, Naim Alkhouri, William Herman, Adrian V. Hernandez, Mary Schleicher, Wen Ye, Srinivasan Dasarathy
Journal: Clinical Gastroenterology and Hepatology (2022)